Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
  • A61K36/233—Bupleurum
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/42—Cucurbitaceae (Cucumber family)
  • A61K36/428—Trichosanthes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
  • A61K36/539—Scutellaria (skullcap)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
  • A61K36/708—Rheum (rhubarb)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
  • A61K36/718—Coptis (goldthread)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
  • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/75—Rutaceae (Rue family)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/88—Liliopsida (monocotyledons)
  • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
  • A61K36/8888—Pinellia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
  • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

• the present invention relates to four methods for preparing a pharmaceutical composition for treating diabetes mellitus (also referred to as diabetes) and the pharmaceutical composition prepared by the methods.
• Diabetes mellitus is a chronic progressive lifelong disease, which is caused by body's metabolic disorder of carbohydrate, protein and lipid with characteristical manifestations of hyperglycemia and glycosuria. It can lead to complications of heart and kidney, blindness and even amputation. Recently, clinical studies showed that morbidity of DM has been rising year by year. By now, the number of patient with DM has amounted to 1.5-hundred millions all over the world. In China, the number of patient with DM has been over 40 millions. In DM cases, most of the patients belong to non-insulin-dependent diabetes mellitus (NIDDM, Type II), and a little belong to insulin-dependent DM (Type I). Thus, most of DM patients need medicine lifelong.
• NIDDM non-insulin-dependent diabetes mellitus
• Type II insulin-dependent DM
• TCM Traditional Chinese medicine
• TCM Traditional Chinese medicine
• Traditional Chinese medicine has a long history in prevention and treatment of DM. After thousand years of practice, much precious experience has been accumulated and the unique academic system has been established.
• a lot of glucose-reducing TCMs have been recorded in the TCM classics, for example Rhizoma Alismatis (Zexie), Rhizoma Anemarrhenae (Zhimu), Radix panacis quinquefolii (Xiyangshen), Radix Puerariae Lobatae (Gegen), Radix Rehmanniae (Dihuang) and pollen grain (Huafen) etc.
• treating DM by TCM is based on clinical symptoms according to “Sanxiao” theory, but has no good therapeutic method in the stage of impaired-glucose-tolerance and early stage of DM.
• DM liver and stomach
• TCM name of DM Xiaoke disease
• Tangminling acts as relieving stagnancy to clear away stomach-heat, nourishing Yin to remove fire and dredging Fu to purge turbidity. It addresses both the symptoms and root cause. Since the gloomy heat has been eliminated, Qi and Yin will be recovered automatically.
• the therapeutic method of DM is to relieve stagnancy to clear away stomach-heat, nourish Yin to remove fire and dredge Fu to purge turbidity.
• Rhizoma Coptidis and Radix et Rhizoma Rhei are used as the monarch drug, in which the Rhizoma Coptidis plays a part of clearing up stomach heat and Radix et Rhizoma Rhei dredging intestinal heat based on the theory of treating sweet by bitter.
• Radix Paeoniae Alba, Radix Scutellariae and Radix Bupleuri are used as the minister drug, where the Radix Paeoniae Alba plays a part of nourishing liver and astringing Yin, assisting the monarch drugs to clear up the heat in “Sanjiao” without damaging Yin; the Radix Bupleuri going into Shaoyang gall meridian and Jueyin liver meridian to clear up the heat of liver and gall and dredging spleen and stomach; the Radix Scutellariae clearing up the heat of lung and liver.
• the Fructus Aurantii Immaturus and raw Fructus Crataegi act as regulating Qi, digesting food and dispersing stasis, working with the Radix et Rhizoma Rhei to facilitate stomach and intestine; the Rhizoma Pinelliae with the Rhizoma Coptidis to render acrid opening and bitter downbearing to open middle warmer. Therefore, all of three drugs are used as assistant drug.
• the Fructus Mume acts as astringing Yin to regenerate body fluid based on the theory of treating sweet by acidity, working with the Radix Trichosanthis to make stomach's Yin vigorous. So it should be called as guide drug.
• a pharmaceutical composition which is composed of Radix Trichosanthis (Tianhuafen), Radix Bupleuri (Chaihu), Fructus Aurantii Immaturus (Zhishi), Radix et Rhizoma Rhei (Dahuang), Rhizoma Pinelliae (Banxia), Radix Scutellariae (Huangqin), Rhizoma Coptidis (Huanglian), Radix Paeoniae Alba (Baishao) and Fructus Mume (Wumei) etc. It has a better efficacy on treating DM.
• the composition has been disclosed in an early Chinese patent application by the applicant (No.
• the objective of the present invention is to provide a pharmaceutical composition for treating DM with the following quantitative formula.
• the pharmaceutical composition is prepared by the methods described below, which can solve the above-mentioned problems in prior arts.
• the pharmaceutical composition of the present invention comprises extracts of the following crude drugs by weight part: 5-40 weight parts of Radix Trichosanthis, 10-30 weight parts of Radix Bupleuri, 3-15 weight parts of Fructus Aurantii Immaturus, 1-6 weight parts of Radix et Rhizoma Rhei, 1-12 weight parts of Rhizoma Pinelliae, 3-15 weight parts of Radix Scutellariae, 1-12 weight parts of Rhizoma Coptidis, 3-15 weight parts of Radix Paeoniae Alba and 5-20 weight parts of Fructus Mume , and optionally comprises pharmaceutically acceptable excipient.
• the pharmaceutical composition can be prepared by any one of the following four methods.
• the first method comprises the following steps:
• the second method comprises the following steps:
• the third method comprises the following steps:
• the fourth method comprises the following steps:
• the composition prepared by the methods of the present invention preferably comprises the following crude drugs: 9 weight parts of Radix Trichosanthis, 12 weight parts of Radix Bupleuri, 9 weight parts of Fructus Aurantii Immaturus, 3 weight parts of Radix et Rhizoma Rhei, 6 weight parts of Rhizoma Pinelliae, 9 weight parts of Radix Scutellariae, 6 weight parts of Rhizoma Coptidis, 9 weight parts of Radix Paeoniae Alba and 9 weight parts of Fructus Mume.
• Fructus Crataegi (Shanzha) can be added into the formulation of the pharmaceutical composition.
• the reasons are as follows: Fructus Crataegi acidifies sweetness and nourishes Yin, not only prevent excessive damage to Yin caused by the dissipation of acridity, but also achieve the purpose of inhibiting sweetness by sour and bitterness. It showed a good effect of dispersing gloomy and clearing up heat when combining with the other crude drugs.
• the pharmaceutical composition preferably comprises the following crude drugs: 5-40 weight parts of Radix Trichosanthis, 10-30 weight parts of Radix Bupleuri, 3-15 weight parts of Fructus Aurantii Immaturus, 1-6 weight parts of Radix et Rhizoma Rhei, 1-12 weight parts of Rhizoma Pinelliae, 3-15 weight parts of Radix Scutellariae, 1-12 weight parts of Rhizoma Coptidis, 3-15 weight parts of Radix Paeoniae Alba, 5-20 weight parts of Fructus Mume and 3-15 weight parts of Fructus Crataegi.
• the pharmaceutical composition of the present invention comprises following crude drugs by weight part: 10-30 weight parts of Radix Trichosanthis, 10-30 weight parts of Radix Bupleuri, 3-15 weight parts of Fructus Aurantii Immaturus, 1-6 weight parts of Radix et Rhizoma Rhei, 1-12 weight parts of Rhizoma Pinelliae, 3-15 weight parts of Radix Scutellariae, 1-12 weight parts of Rhizoma Coptidis, 3-15 weight parts of Radix Paeoniae Alba, 5-20 weight parts of Fructus Mume and 3-15 weight parts of Fructus Crataegi.
• the pharmaceutical composition of the present invention comprises following crude drugs: 30 weight parts of Radix Trichosanthis, 12 weight parts of Radix Bupleuri, 9 weight parts of Fructus Aurantii Immaturus, 3 weight parts of Radix et Rhizoma Rhei, 6 weight parts of Rhizoma Pinelliae, 9 weight parts of Radix Scutellariae, 6 weight parts of Rhizoma Coptidis, 9 weight parts of Radix Paeoniae Alba, 15 weight parts of Fructus Mume and 9 weight parts of Fructus Crataegi , or the pharmaceutical composition of the present invention comprises following crude drugs by weight part: 15 weight parts of Radix Trichosanthis, 12 weight parts of Radix Bupleuri, 9 weight parts of Fructus Aurantii Immaturus, 3 weight parts of Radix et Rhizoma Rhei, 6 weight parts of Rhizoma Pinelliae, 9 weight parts of Radix Scutellariae, 6 weight parts of Rhizoma Coptid
• the following steps are preferable:
• the extraction-by-reflux is preferably performed twice with water of 10 times ( ⁇ 10 fold) the weight of the crude drugs for 1.5 hour per time.
• the extract liquid is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1;
• the concentration of the added ethanol preferably is 90-100%, more preferably 95%.
• the concentrated extract liquid contains 70% ethanol.
• the content of the active components significantly increased and the content impurities are remarkably decreased. Hence, the administration dosage is decreased.
• the extraction-by-reflux is preferably performed twice with water of 10 times ( ⁇ 10 fold) the weight of the crude drugs for 1.0 hour per time.
• the macro-porous resin preferably is AB-8 type; the weight ratio of the resin to the crude drugs preferably is 1:1.5-1:3, more preferably 1:2.
• the extract liquid is loaded preferably in a speed of 4-6 times the column volume per hour.
• the amount of the water for washing preferably is 4-6 times the column volume.
• the concentration of ethanol for washing preferably is 80-95%, more preferably 90%; the volume of ethanol for washing preferably is 2-5 times the column volume.
• the ethanol is recovered under reduced pressure preferably at a temperature of 60-80° C. By recovering ethanol under reduced pressure, an extract is obtained with a relative density of 1.25-1.35, preferably 1.30.
• Water-extraction is adopted in the above method, ensuring water-soluble active components such as saikosaponin, berberin(berberine hydrochloride), baicalin, chrysophanol, paeoniflorin and synephrine etc., can be extracted from the crude drug to a greatest extent.
• many efficient extraction steps are used, including macro-porous resin adsorption and washing by water to remove impurities, and eluting active components with ethanol aqueous solution. By these means, the majority of impurities can be removed and the active components can be retained.
• the pharmaceutical composition prepared by the above method is characteristic of remarkably increased contents of the active components and greatly decreased contents of impurities, and the administration dosage is decreased correspondingly. Meanwhile, the stability between batches is ensured.
• the concentration of the ethanol is 75-90%, preferably 80%; and preferably, the extraction-by-reflux is performed twice with ethanol of 10 times the weight of the crude drugs of the step (b) for 1.5 hour per time.
• the extraction-by-reflux preferably is performed twice with water of 10 times the weight of the total weight of the crude drugs of the step (c) and the drug residue of step (b) for 1.5 hour per time; the extract liquid is preferably concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1.
• the concentration of the added ethanol preferably is 90-100%, more preferably 95%; after adding ethanol, the concentrated extract liquid contains 65-75%, preferably 70% ethanol.
• the extraction-by-reflux is performed twice with water of 10 times the weight of the Radix Scutellariae for 1 hour per time; the extract liquid is preferably kept at 75-85° C., more preferably at 80° C.
• the extraction-by-reflux is preferably performed twice with ethanol of 10 times the weight of the Rhizoma Coptidis for 2 hours per time; the concentration of ethanol preferably is 70-85%, more preferably 75%.
• the pH is preferably adjusted by concentrated hydrochloride acid.
• the extraction-by-reflux is preferably performed twice with water of 10 times the weight of the other crude drugs for 1 hour per time; the combined extract liquid is concentrated into a concentrated extract liquid with a relative density of 1.03-1.07, preferably 1.05; after adding ethanol, recovering ethanol to give an extract preferably with a relative density of 1.25-1.35, more preferably 1.30.
• the Radix Scutellariae, Rhizoma Coptidis and the other crude drugs are extracted respectively.
• the water extraction or ethanol extraction is selected according to their different chemical properties, and then pH value is adjusted.
• the content of the active components significantly increased and the content of impurities are remarkably decreased. Hence, the administration dosage is decreased.
• a pharmaceutical composition having the above formulation for treatment of diabetes mellitus can be prepared.
• the composition of the present invention can be prepared by conventional method into any one of conventional dosage forms with conventionally used excipients known in prior arts.
• the above crude drugs can be administrated in many manners: being powdered and infused with water; being prepared into an extract, dried, pulverized, sifted, powdered and infused with water, or the obtained extract being prepared into tablet or capsule and administrated orally, or the obtained extract being prepared into injection etc.
• these are not intended to limit the scope of the present invention.
• the pharmaceutical composition prepared by the method of the present invention has the function of lowering blood sugar, having a good effect of treating DM clinically.
• the concentration of ethanol or the content of ethanol (the content of ethanol in the system) is expressed by percentage, it refers to volume percentage except where otherwise noted.
• Formulation 750 g of Radix Trichosanthis, 1500 g of Radix Bupleuri, 450 g of Fructus Aurantii Immaturus, 150 g of Radix et Rhizoma Rhei, 150 g of Rhizoma Pinelliae, 450 g of Radix Scutellariae, 150 g of Rhizoma Coptidis, 450 g of Radix Paeoniae Alba and 750 g of Fructus Mume.
• composition is prepared by the following method:
• the above nine crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 90% ethanol is added to make the content of ethanol to 65%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 75% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 90% ethanol is added to make the content of ethanol to 65%, filtering for further use.
• composition is prepared by the following method:
• the above nine crude drugs are extracted twice by reflux with water, adding 48.5 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 3.2 kg of AB-8 type macro-porous adsorption resin in a speed of 4 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 80% ethanol of 2 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 80° C. under reduced pressure to give an extract with a relative density of 1.25.
• Vacuum-dried is performed at 70° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Lactose is added into the screened dry powder to prepare into capsules.
• composition is prepared by the following method:
• Formulation 1200 g of Radix Trichosanthis, 900 g of Radix Bupleuri, 450 g of Fructus Aurantii Immaturus, 180 g of Radix et Rhizoma Rhei, 360 g of Rhizoma Pinelliae, 450 g of Radix Scutellariae, 360 g of Rhizoma Coptidis, 450 g of Radix Paeoniae Alba and 600 g of Fructus Mume.
• composition is prepared by the following method:
• the above nine crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, anhydrous ethanol is added to make the content of ethanol to 75%. Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 90% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1.
• Anhydrous ethanol is added to make the content of ethanol to 75%, filtering for further use.
• composition is prepared by the following method:
• the above nine crude drugs are extracted twice by reflux with water, adding 49.5 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 1.7 kg of AB-8 type macro-porous adsorption resin in a speed of 6 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 95% ethanol of 5 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 70° C. under reduced pressure to give an extract with a relative density of 1.35.
• Vacuum-dried is performed at 90° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Starch is added into the screened dry powder to prepare into tablets.
• composition is prepared by the following method:
• Formulation 630 g of Radix Trichosanthis, 840 g of Radix Bupleuri, 630 g of Fructus Aurantii Immaturus, 210 g of Radix et Rhizoma Rhei, 420 g of Rhizoma Pinelliae, 630 g of Radix Scutellariae, 420 g of Rhizoma Coptidis, 630 g of Radix Paeoniae Alba and 630 g of Fructus Mume.
• composition is prepared by the following method:
• the above nine crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 95% ethanol is added to make the content of ethanol to 70%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 80% ethanol 10 of times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 95% ethanol is added to make the content of ethanol to 70%, filtering for further use.
• composition is prepared by the following method:
• the above nine crude drugs are extracted twice by reflux with water, adding 50.4 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 2.52 kg of AB-8 type macro-porous adsorption resin in a speed of 5 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 90% ethanol of 3 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 70° C. under reduced pressure to give an extract with a relative density of 1.30.
• Vacuum-dried is performed at 80° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Microcrystalline cellulose is added into the screened dry powder to prepare into concentrated pills.
• composition is prepared by the following method:
• Formulation 750 g of Radix Trichosanthis, 1500 g of Radix Bupleuri, 450 g of Fructus Aurantii Immaturus, 150 g of Radix et Rhizoma Rhei, 150 g of Rhizoma Pinelliae, 450 g of Radix Scutellariae, 150 g of Rhizoma Coptidis, 450 g of Radix Paeoniae Alba, 750 g of Fructus Mume and 450 g of Fructus Crataegi.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 90% ethanol is added to make the content of ethanol to 65%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 75% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 90% ethanol is added to make the content of ethanol to 65%, filtering for further use.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water, adding 52.5 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 3.5 kg of AB-8 type macro-porous adsorption resin in a speed of 4 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 80% ethanol of 2 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 80° C. under reduced pressure to give an extract with a relative density of 1.35.
• Vacuum-dried is performed at 70° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Lactose is added into the screened dry powder to prepare into capsules.
• composition is prepared by the following method:
• Formulation 1200 g of Radix Trichosanthis, 900 g of Radix Bupleuri, 450 g of Fructus Aurantii Immaturus, 180 g of Radix et Rhizoma Rhei, 360 g of Rhizoma Pinelliae, 450 g of Radix Scutellariae, 360 g of Rhizoma Coptidis, 450 g of Radix Paeoniae Alba, 600 g of Fructus Mume and 450 g of Fructus Crataegi.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, anhydrous ethanol is added to make the content of ethanol to 75%. Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 90% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1.
• Anhydrous ethanol is added to make the content of ethanol to 75%, filtering for further use.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water, adding 54 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 1.8 kg of AB-8 type macro-porous adsorption resin in a speed of 6 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 95% ethanol of 5 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 70° C. under reduced pressure to give an extract with a relative density of 1.25.
• Vacuum-dried is performed at 90° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Lactose is added into the screened dry powder to prepare into capsules.
• composition is prepared by the following method:
• Formulation 833 g of Radix Trichosanthis, 667 g of Radix Bupleuri, 500 g of Fructus Aurantii Immaturus, 167 g of Radix et Rhizoma Rhei, 333 g of Rhizoma Pinelliae, 500 g of Radix Scutellariae, 333 g of Rhizoma Coptidis, 500 g of Radix Paeoniae Alba, 833 g of Fructus Mume and 500 g of Fructus Crataegi.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 95% ethanol is added to make the content of ethanol to 70%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 80% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 95% ethanol is added to make the content of ethanol to 70%, filtering for further use.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water, adding 51.7 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 2.6 kg of AB-8 type macro-porous adsorption resin in a speed of 5 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 90% ethanol of 3 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 70° C. under reduced pressure to give an extract with a relative density of 1.30.
• Vacuum-dried is performed at 80° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Microcrystalline cellulose is added into the screened dry powder to prepare into concentrated pills.
• composition is prepared by the following method:
• Formulation 500 g of Radix Trichosanthis, 750 g of Radix Bupleuri, 500 g of Fructus Aurantii Immaturus, 250 g of Radix et Rhizoma Rhei, 500 g of Rhizoma Pinelliae, 500 g of Radix Scutellariae, 500 g of Rhizoma Coptidis, 500 g of Radix Paeoniae Alba, 500 g of Fructus Mume and 500 g of Fructus Crataegi.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 95% ethanol is added to make the content of ethanol to 70%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 80% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 95% ethanol is added to make the content of ethanol to 70%, filtering for further use.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water, adding 50 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 2.5 kg of AB-8 type macro-porous adsorption resin in a speed of 4 times the column volume per hour. After washing with water of 5 times the column volume, the eluate is discarded. Then, the washing is conducted again with 92% ethanol of 4 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 75° C. under reduced pressure to give an extract with a relative density of 1.25. Vacuum-dried is performed at 85° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Dextrin is added into the screened dry powder to prepare into tablets.
• composition is prepared by the following method:
• Formulation 1200 g of Radix Trichosanthis, 800 g of Radix Bupleuri, 600 g of Fructus Aurantii Immaturus, 200 g of Radix et Rhizoma Rhei, 400 g of Rhizoma Pinelliae, 400 g of Radix Scutellariae, 200 g of Rhizoma Coptidis, 400 g of Radix Paeoniae Alba, 400 g of Fructus Mume and 400 g of Fructus Crataegi.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 90% ethanol is added to make the content of ethanol to 68%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 85% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 90% ethanol is added to make the content of ethanol to 68%, filtering for further use.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water, adding 50 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 2.0 kg of AB-8 type macro-porous adsorption resin in a speed of 6 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 92% ethanol of 3 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 65° C. under reduced pressure to give an extract with a relative density of 1.30.
• Vacuum-dried is performed at 75° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Lactose is added into the screened dry powder to prepare into capsules.
• composition is prepared by the following method:
• Formulation 1000 g of Radix Trichosanthis, 600 g of Radix Bupleuri, 600 g of Fructus Aurantii Immaturus, 250 g of Radix et Rhizoma Rhei, 300 g of Rhizoma Pinelliae, 500 g of Radix Scutellariae, 300 g of Rhizoma Coptidis, 500 g of Radix Paeoniae Alba, 500 g of Fructus Mume and 300 g of Fructus Crataegi.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water of 10 times the weight of the crude drugs, 1.5 hour per time.
• the extract liquid is filtered, concentrated under reduced pressure into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1, 99% ethanol is added to make the content of ethanol to 74%.
• Obtained extract liquid is filtered and concentrated under reduced pressure into a dense extract.
• composition is prepared by the following method:
• the following six crude drugs ( Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis ) are extracted twice by reflux with 90% ethanol of 10 times the weight of the crude drugs for 1.5 hour per time to give the extract liquid (1) and the drug residue.
• the extract liquid (1) is filtered for further use.
• extract liquid (2) is concentrated into a concentrated extract liquid with the final volume (L) to the initial weight of the crude drugs (kg) in ratio of 1:1. 99% ethanol is added to make the content of ethanol to 74%, filtering for further use.
• composition is prepared by the following method:
• the above ten crude drugs are extracted twice by reflux with water, adding 48.5 kg water in each one-hour extraction; cooling down the extract liquid, filtering and combining.
• the combined filtrate is loaded onto 1.7 kg of AB-8 type macro-porous adsorption resin in a speed of 5 times the column volume per hour.
• the eluate is discarded.
• the washing is conducted again with 85% ethanol of 5 times the column volume, and the ethanol eluate is combined.
• the ethanol is recovered from the combined ethanol eluate at 70° C. under reduced pressure to give an extract with a relative density of 1.35.
• Vacuum-dried is performed at 90° C. to obtain a dry extract, which is pulverized and screened through 80-mesh sieve. Lactose is added into the screened dry powder to prepare into capsules.
• composition is prepared by the following method:
• Streptozotocin (STZ) was purchased from Sigma (USA) with batch number of 024K1211.
• Anhydrous citric acid (C 6 H 8 O 7 .H 2 O) was purchased from Tianjin Chemical Reagent No. 1 Factory with batch number of 011121.
• Sodium citrate Na 3 C 6 H 5 O 7 .2H 2 O was purchased from Tianjin Chemical Reagent No. 1 Factory with batch number of 011219.
• Metformin 250 mg/tablet was purchased from Tianjin Pacific Ocean Pharmaceutical Co., Ltd. with batch number of 040121.
• Tested drugs (TL-1, TL-2 and TL-3) were powder of the extract respectively prepared by Examples 3, 8 and 9.
• Stable blood glucose meter (One-Touch Ultra) was purchased from Lifescan Inc. (USA) with certificate number of 20032400735.
• SD rats were fasted overnight after one-week adaptation, intraperitoneal and injected a solution of 2% (W/V) STZ prepared with 0.1 mmol/L citric acid buffer solution (pH 4.4) (65 mg/kg). Three days later, the blood was sampled from tail vein to assay blood glucose. Those animals with blood glucose level equal to or higher than 16.7 mmol/L were considered to be successful model.
• the modeled rats were randomly divided into model group, Metformin (125 mg/kg) group and different treatment groups (corresponding to 15.5 g crude drugs/kg). After one-week adaptation and the blood glucose detection, rats were administered by gastric infusion, once a day. All of the drugs were diluted with physiological saline to prepare into suspension for administration. Animals were free to access of food and water during the 15-day testing period. At the seventh and fourteenth day after administration, the rats were fasted for two hours after administration. Respectively, blood was sampled from tail vein to assay blood glucose with blood glucose meter (one-touch ultra). At the same time, the body weights of the rats were measured.
• Results were expressed as mean ⁇ SD ( X ⁇ SD), and t-test was used to evaluate the significant difference of measurement data between two groups.

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